Methods of food intake management

Abstract

Methods for regulating food intake in a human subject; for improving a compliance of a human subject to caloric restriction; and for reducing a desire of a human subject to consume fats, utilizing H 1 -receptor agonists that have a pharmacological half-life that allows an efficient treatment regime thereof are disclosed. The methods can be efficiently used for treating conditions such as overeating, overweight, obesity, binge eating disorder, night eating syndrome, obsessive eating, compulsive eating and bulimia, as well as conditions associated with metabolic derangement such as dyslipidemia.

1 . A method of treating of a condition in which regulating a food intake in a human subject is beneficial, the method comprising administering to the subject a therapeutically effective amount of an H 1  agonist, said condition being selected from the group consisting of overeating, overweight, an eating disorder and a disorder caused or exacerbated thereby.  
   
   
       2 . The method of  claim 1 , wherein said H 1  agonist is betahistine or pharmaceutically acceptable salt thereof.  
   
   
       3 . The method of  claim 1 , wherein said H 1  agonist is a betahistine metabolite.  
   
   
       4 . The method of  claim 3 , wherein said betahistine metabolite is 2-(2-aminoethyl)-pyridine.  
   
   
       5 . The method of  claim 2 , wherein said betahistine salt is selected from the group consisting of betahistine dihydrochloride, betahistine mesilate, and betahistine trimebutine maleate.  
   
   
       6 . The method of  claim 1 , wherein said H 1  agonist is a betahistine derivative.  
   
   
       7 . The method of  claim 6 , wherein said betahistine derivative is selected from the group of compounds represented by formula I:  
     
       
         
         
             
             
         
       
       wherein each of R 1 -R 12  is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl and aryl.  
     
   
   
       8 . The method of  claim 1 , wherein said therapeutically effective amount ranges from about 2 mg per unit dosage to about 96 mg per unit dosage.  
   
   
       9 . The method of  claim 8 , wherein said therapeutically effective amount ranges from about 10 mg per day to about 50 mg per day.  
   
   
       10 . The method of  claim 1 , wherein said administering is effected from about 1 to about 4 times per day.  
   
   
       11 . The method of  claim 1 , wherein said administering is effected according to the development of hunger of the subject.  
   
   
       12 . The method of  claim 1 , wherein said administering is performed such that a decrease of the body weight of the subject that ranges from about 1 to about 5 percent is effected, without restricting the food intake of the subject.  
   
   
       13 . The method of  claim 1 , wherein said condition is associated with a psychological factor.  
   
   
       14 . The method of  claim 13 , wherein said condition comprises binge eating disorder, night eating syndrome, obsessive eating, compulsive eating and bulimia.  
   
   
       15 . The method of  claim 1 , wherein said eating disorder is selected from the group consisting of bulimia and binge eating disorder.  
   
   
       16 . The method of  claim 1 , wherein said disorder caused by or exacerbated by said condition is selected from the group consisting of a muscoskeletal disorder, a cardiovascular disorder, a dermatological disorder, a sleep disorder, a metabolic condition, diabetes and a diabetes-related condition.  
   
   
       17 . The method of  claim 1 , wherein said H 1  agonist forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier.  
   
   
       18 . The method of  claim 17 , wherein said pharmaceutical composition is a slow-release composition.  
   
   
       19 . The method of  claim 1 , further comprising administering to the subject a therapeutically effective amount of an additional active agent.  
   
   
       20 . The method of  claim 19 , wherein said additional active agent is selected from the group consisting of a non-steroidal anti-inflammatory drug, a muscle relaxant, an antigout agent, an immunosuppressant, a drug affecting bone mineralization, an alpha-adrenergic blocking drugs, an angiotensin-converting enzyme inhibitor, an antiarrhythmic drug, an anticoagulant, an antiplatelet, a thrombolytic, a beta-adrenergic blocking drug, a calcium channel blocker, a centrally acting drug, a digitalis drug, a nitrate, a peripheral adrenergic antagonist, a vasodilator, an acne medication, an antipruretic agent, a corticosteroid, an anti-psoriasis agent, an anti-eczema agent, a hypnotic, an anti-depressant, an anti-histamine, a sulfonylurea, a meglitinide, a biguanide, a thiazolidinedione, an alpha-glucosidase inhibitor, a PPAR-gamma antagonist, insulin, a fibrate, an HMG-CoA reductase inhibitor, a bile acid sequestrant, a nutritional supplement, a cholesterol absorption inhibitor, nicotinic acid, a derivative, analog and metabolite thereof, and any mixture thereof.  
   
   
       21 . The method of  claim 19 , wherein said additional active agent is a weight control agent.  
   
   
       22 . The method of  claim 1 , being for inducing weight loss.  
   
   
       23 . The method of  claim 1 , being for maintaining weight loss or preventing a weight gain after or during a weight reducing diet.  
   
   
       24 . The method of  claim 1 , being for preventing weight gain in a subject having a condition associated with weight gain.  
   
   
       25 . A method of improving a compliance of a human subject to caloric restriction, the method comprising administering to the subject a therapeutically effective amount of an H 1  agonist.  
   
   
       26 . The method of  claim 25 , wherein said H 1  agonist is betahistine or pharmaceutically acceptable salt thereof.  
   
   
       27 . The method of  claim 25 , wherein said H 1  agonist is a betahistine metabolite.  
   
   
       28 . The method of  claim 27 , wherein said betahistine metabolite is 2-(2-aminoethyl)-pyridine.  
   
   
       29 . The method of  claim 26 , wherein said betahistine salt is selected from the group consisting of betahistine dihydrochloride, betahistine mesilate, and betahistine trimebutine maleate.  
   
   
       30 . The method of  claim 25 , wherein said H 1  agonist is a betahistine derivative.  
   
   
       31 . The method of  claim 30 , wherein said betahistine derivative is selected from the group of compounds represented by formula I:  
     
       
         
         
             
             
         
       
       wherein each of R 1 -R 12  is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl and aryl.  
     
   
   
       32 . The method of  claim 25 , wherein said therapeutically effective amount ranges from about 2 mg per unit dosage to about 96 mg per unit dosage.  
   
   
       33 . The method of  claim 25 , wherein said administering is effected from about 1 to about 4 times per day.  
   
   
       34 . The method of  claim 25 , wherein said administering is effected according to the development of hunger of the subject.  
   
   
       35 . The method of  claim 25 , wherein said H 1  agonist forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier.  
   
   
       36 . A method of reducing a desire of a human subject to consume fats, the method comprising administering to the subject a therapeutically effective amount of an H 1  agonist.  
   
   
       37 . The method of  claim 36 , wherein said H 1  agonist is betahistine or pharmaceutically acceptable salt thereof.  
   
   
       38 . The method of  claim 36 , wherein said H 1  agonist is a betahistine metabolite.  
   
   
       39 . The method of  claim 38 , wherein said betahistine metabolite is 2-(2-aminoethyl)-pyridine.  
   
   
       40 . The method of  claim 37 , wherein said betahistine salt is selected from the group consisting of betahistine dihydrochloride, betahistine mesilate, and betahistine trimebutine maleate.  
   
   
       41 . The method of  claim 36 , wherein said H 1  agonist is a betahistine derivative.  
   
   
       42 . The method of  claim 41 , wherein said betahistine derivative is selected from the group of compounds represented by formula I:  
     
       
         
         
             
             
         
       
       wherein each of R 1 -R 12  is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl and aryl.  
     
   
   
       43 . The method of  claim 36 , wherein said therapeutically effective amount ranges from about 2 mg per unit dosage to about 96 mg per unit dosage.  
   
   
       44 . The method of  claim 36 , wherein said administering is effected from about 1 to about 4 times per day.  
   
   
       45 . The method of  claim 36 , wherein said administering is effected according to the development of hunger of the subject.  
   
   
       46 . The method of  claim 36 , wherein said H 1  agonist forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier.  
   
   
       47 . A method of preventing or reducing weight gain in a subject, the method comprising administering to the subject a therapeutically effective amount of an H 1  agonist, said weight gain being associated with a drug treatment, is due to cessation of smoking and/or occurs during a holiday season, said drug being selected from the group consisting of a mood stabilizer, an anti-convalsunt, a calcium channel blocker, a proton pump inhibitor, an antidiabetic agent, an antihypertensive, a hormone, and an anti-smoking medication.  
   
   
       48 . The method of  claim 47 , wherein said hormone comprises a steroid hormone.  
   
   
       49 . The method of  claim 47 , wherein said weight gain causes a metabolic disorder.  
   
   
       50 . The method of  claim 49 , wherein said metabolic disorder is selected from the group consisting of metabolic syndrome, diabetes and dyslipidemia.  
   
   
       51 . The method of  claim 47 , wherein said H 1  agonist is betahistine or pharmaceutically acceptable salt thereof.  
   
   
       52 . The method of  claim 47 , wherein said H 1  agonist is a betahistine metabolite.  
   
   
       53 . The method of  claim 52 , wherein said betahistine metabolite is 2-(2-aminoethyl)-pyridine.  
   
   
       54 . The method of  claim 51 , wherein said betahistine salt is selected from the group consisting of betahistine dihydrochloride, betahistine mesilate, and betahistine trimebutine maleate.  
   
   
       55 . The method of  claim 47 , wherein said H 1  agonist is a betahistine derivative.  
   
   
       56 . The method of  claim 55 , wherein said betahistine derivative is selected from the group of compounds represented by formula I:  
     
       
         
         
             
             
         
       
       wherein each of R 1 -R 12  is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl and aryl.  
     
   
   
       57 . The method of  claim 47 , wherein said therapeutically effective amount ranges from about 2 mg per unit dosage to about 96 mg per unit dosage.  
   
   
       58 . The method of  claim 47 , wherein said administering is effected from about 1 to about 4 times per day.  
   
   
       59 . The method of  claim 47 , wherein said administering is effected according to the development of hunger of the subject.  
   
   
       60 . The method of  claim 47 , wherein said H 1  agonist forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier.  
   
   
       61 . The method of  claim 60 , wherein said pharmaceutical composition is a slow-release composition.  
   
   
       62 . The method of  claim 47 , further comprising administering to the subject a therapeutically effective amount of an additional active agent.  
   
   
       63 . The method of  claim 62 , wherein said additional active agent is selected from the group consisting of a non-steroidal anti-inflammatory drug, a muscle relaxant, an antigout agent, an immunosuppressant, a drug affecting bone mineralization, an angiotensin-converting enzyme inhibitor, an antiarrhythmic drug, an anticoagulant, an antiplatelet, a thrombolytic, a centrally acting drug, a digitalis drug, a nitrate, a peripheral adrenergic antagonist, a vasodilator, an acne medication, an antipruretic agent, an anti-psoriasis agent, an anti-eczema agent, a hypnotic, an anti-histamine, a fibrate, an HMG-CoA reductase inhibitor, a nutritional supplement, a bile acid sequestrant, a cholesterol absorption inhibitor, nicotinic acid, a derivative, analog and metabolite thereof, and any mixture thereof.  
   
   
       64 . The method of  claim 62 , wherein said additional active agent is a weight control agent.